The immediate goal of the candidate, Robin W. Allison, DVM, is to complete a mentored training program in retrovirus pathogenesis research which will culminate in both the PhD degree and the opportunity for continued postdoctoral study. Dr. Allison's long-term goal is to become a principal investigator employing animal models to investigate the pathogenesis and therapy of HIV. The research training program will be conducted in the Retrovirus Research Laboratory at Colorado State University, under the guidance of the sponsor Dr. Edward A. Hoover. The candidate's training plan includes laboratory and didactic training in contemporary molecular techniques and research methods, applied to an animal model of AIDS. We propose to use an established feline immunodeficiency virus (FIV) model of mother-to-offspring lentivirus transmission to investigate perinatal HIV treatment strategies and the biology of milk-borne virus transmission. The three specific aims to be addressed are: (1) to determine whether antiviral therapy of mother cats (queens) and their kittens with the drug PMPA [9- 2(phosphonylmethoxypropyl)adenine] will prevent perinatal FIV transmission; (2) to investigate the dynamics of cell-associated and cell-free virus in milk, and identify potential cellular origins of virus in mammary tissues; (3) to evaluate therapeutic intervention for milk-borne lentivirus transmission. Aims 1 and 2 will be addressed using FIV+ queens and their kittens, which will be treated pre-and postpartum with either PMPA or placebo. Effects of treatment and viral presence in milk will be detected by assaying PBMC, milk cells, plasma, and milk supernatant for virus by several methods at multiple timepoints. Kittens will be necropsied 4 weeks after cessation of therapy and tissues assayed for virus. Cellular sources of milk virus will be sought by in situ hybridization and immunohistochemistry performed on serial mammary gland biopsies and milk cells. To address Aim 3, nave kittens will be foster-nursed by FIV+ queens, and either PMPA- or sham-treated until weaning. These animals will be monitored for virus expression during treatment, and necropsied 4 weeks after cessation of therapy. Results of these studies will provide new insight into the biology of milk-borne virus, and contribute information pertinent to the design of intervention strategies for HIV vertical transmission.